Extracellular NAMPT/visfatin causes p53 deacetylation via NAD production and SIRT1 activation in breast cancer cells

Behrouzfar, Kiarash; Alaee, Mohammad Reza; Nourbakhsh, Mitra; Gholinejad, Zafar; Golestani, Abolfazl

doi:10.1002/cbf.3279

Cited by 38 publications

(25 citation statements)

References 58 publications

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“…In melanoma cells, NAMPT regulation of the E2F family member 2 was shown to impact transcription and translation of SIRT1, and genetic or pharmacologic loss of NAMPT activity resulted in activation of TP53 and apoptotic cell death (79). A similar regulatory network has been described in breast cancer cells where increased SIRT1 activity and induction of deacetylation of TP53 were observed upon exposure to the extracellular form of NAMPT (80).…”

Section: Sirtuin Functionmentioning

confidence: 72%

Beyond Energy Metabolism: Exploiting the Additional Roles of NAMPT for Cancer Therapy

Heske

2020

Front. Oncol.

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Tumor cells have increased requirements for NAD +. Thus, many cancers exhibit an increased reliance on NAD + production pathways. This dependence may be exploited therapeutically through pharmacological targeting of NAMPT, the rate-limiting enzyme in the NAD + salvage pathway. Despite promising preclinical data using NAMPT inhibitors in cancer models, early NAMPT inhibitors showed limited efficacy in several early phase clinical trials, necessitating the identification of strategies, such as drug combinations, to enhance their efficacy. While the effect of NAMPT inhibitors on impairment of energy metabolism in cancer cells has been well-described, more recent insights have uncovered a number of additional targetable cellular processes that are impacted by inhibition of NAMPT. These include sirtuin function, DNA repair machinery, redox homeostasis, molecular signaling, cellular stemness, and immune processes. This review highlights the recent findings describing the effects of NAMPT inhibitors on the non-metabolic functions of malignant cells, with a focus on how this information can be leveraged clinically. Combining NAMPT inhibitors with other therapies that target NAD +-dependent processes or selecting tumors with specific vulnerabilities that can be co-targeted with NAMPT inhibitors may represent opportunities to exploit the multiple functions of this enzyme for greater therapeutic benefit.

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Section: Sirtuin Functionmentioning

confidence: 72%

Beyond Energy Metabolism: Exploiting the Additional Roles of NAMPT for Cancer Therapy

Heske

2020

Front. Oncol.

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“…Numerous previous studies on established cell lines have shown that eNampt exerts a stimulating effect on the rate of proliferation of different cancer cells. Such action has been observed, inter alia, in the case of MCF-7 and MDA-MB-231 breast cancer cells [23,24], PC3 prostate cancer cell [25] Me45 melanoma cell [18], hepatocellular carcinoma (HCC) cells [26], AGS gastric cancer cell line [27] Ishikawa and KLE endometrial carcinoma cell lines [28]. No Nampt receptor has been identified so far and the stimulating effect of Nampt on proliferation most probably occurs through AKT/PI3K, ERK/ MAPK and GSK-3β proteins signaling pathways [23,25,26,28].…”

Section: Discussionmentioning

confidence: 81%

“…As known, Nampt plays a central role in the systemic regulation of NAD biosynthesis in cells, hence it can also regulate their proliferation. In the available literature there are many publications that this cytokine exerts dose-dependent stimulating effect on proliferative activity, mainly of cancer cells [18,[23][24][25][26][27][28]. This stimulation occurred probably through AKT/PI3K, ERK/MAPK and GSK-3β proteins [23,25,26,28].…”

Section: Introductionmentioning

confidence: 99%

Nampt (Visfatin) Influence on Proliferative Activity of Normal Rat Adrenocortical Cells and Human Adrenal Corticocarcinoma Nci-H295r Cells

Celichowski

Jopek

Szyszka

et al. 2018

Medical Journal of Cell Biology

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Nampt (Nicotinamidephosphoribosyltransferase - also known as visfatin/PBEF) is the enzyme that regulates the NAD+ level, therefore influencing many metabolic pathways within the cells. As circulating cytokine, extracellular Nampt (eNampt) exerts pro-inflammatory, pro-chemotactic, pro-angiogenic and insulin-like effects; however the mechanism of eNampt action is still unclear.Earlier studies have shown that eNampt exerts a stimulating effect on the proliferation of many cancer cell lines. However, the effect of this cytokine on cell proliferation in primary culture is little known. Therefore, the aim of the study was to analyse the influence of eNampt on the proliferation of rat adrenocortical cells in primary culture and to investigate similar influence of eNampt on the line H295R of human adrenal corticocarcinoma cells. Proliferation of the examined cells was assessed using the RTCA (Real Time Cell Analyzer) method. The obtained results indicate that eNampt stimulates the proliferation of H295R cells, but does not change the proliferation of cultured rat adrenocortical cells. In primary culture of rat adrenocortical cells, Fk866 (specific Nampt inhibitor) does not modify the rate of proliferation of tested cells. In H295R cells the addition of Fk866 alone inhibits proliferative activity and stimulates apoptosis. Fk866 also inhibits the stimulating effect of eNampt on H295R cell proliferation.

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“…Visfatin increases both extracellular and intracellular nicotinamide adenine dinucleotide (NAD) concentration in breast cancer cells, which causes upregulation of silent information regulator 1 (SIRT1) activity and p53 deacetylation. SIRT1 is implicated in blocking senescence and apoptosis and promoting cancer growth ( 127 ).…”

Section: Bmas and Mechanisms Responsible For Macrometastasis And Outgmentioning

confidence: 99%

Bone Marrow Adipocytes, Adipocytokines, and Breast Cancer Cells: Novel Implications in Bone Metastasis of Breast Cancer

Liu

Zhao

2020

Front. Oncol.

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Accumulating discoveries highlight the importance of interaction between marrow stromal cells and cancer cells for bone metastasis. Bone is the most common metastatic site of breast cancer and bone marrow adipocytes (BMAs) are the most abundant component of the bone marrow microenvironment. BMAs are unique in their origin and location, and recently they are found to serve as an endocrine organ that secretes adipokines, cytokines, chemokines, and growth factors. It is reasonable to speculate that BMAs contribute to the modification of bone metastatic microenvironment and affecting metastatic breast cancer cells in the bone marrow. Indeed, BMAs may participate in bone metastasis of breast cancer through regulation of recruitment, invasion, survival, colonization, proliferation, angiogenesis, and immune modulation by their production of various adipocytokines. In this review, we provide an overview of research progress, focusing on adipocytokines secreted by BMAs and their potential roles for bone metastasis of breast cancer, and investigating the mechanisms mediating the interaction between BMAs and metastatic breast cancer cells. Based on current findings, BMAs may function as a pivotal modulator of bone metastasis of breast cancer, therefore targeting BMAs combined with conventional treatment programs might present a promising therapeutic option.

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Extracellular NAMPT/visfatin causes p53 deacetylation via NAD production and SIRT1 activation in breast cancer cells

Cited by 38 publications

References 58 publications

Beyond Energy Metabolism: Exploiting the Additional Roles of NAMPT for Cancer Therapy

Beyond Energy Metabolism: Exploiting the Additional Roles of NAMPT for Cancer Therapy

Nampt (Visfatin) Influence on Proliferative Activity of Normal Rat Adrenocortical Cells and Human Adrenal Corticocarcinoma Nci-H295r Cells

Bone Marrow Adipocytes, Adipocytokines, and Breast Cancer Cells: Novel Implications in Bone Metastasis of Breast Cancer

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